The long-term goal of this proposal is to develop selective estrogen receptor modulators for the treatment of hormone dependent medical disorders such as breast cancer and osteoporosis. Breast cancer is currently the second leading cause of cancer deaths among women. If detected and treated early without spreading beyond the breast, more than 90% of women will survive. Tamoxifen, a non-steroidal anti-estrogen, has been in clinical use for the treatment of beast cancer for almost 25 years. However, tamoxifen suffers from its ability to increase the risk of endometrial cancer, formation of blood clots in the liver, and the frequent occurrence of hot flashes among post-menopausal women. The cancer cells also develop a resistance to long term tamoxifen treatment. Therefore, there is a need exhibited by tamoxifen. In recent years, several steroidal and non-steroidal anti-estrogens have been developed. A few of these analogs antagonize the effect of estrogen on breast and utering tissues while mimicking the effects of estrogen on bone and the cardiovascular system. These were, thus, classified as Selective Estrogen Receptor Modulators (SERM). One such compound, raloxifene, is already in use for the treatment of osteoporosis. Our aims in his application are 1) design and synthesis of newer selective estrogen receptor modulators and 2) demonstrate that these analogs are effective binders of estrogen receptors and inhibit the proliferation of MC-7 cells. PROPOSED COMMERCIAL APPLICATION: The research would lead to development of novel selective estrogen receptor modulators. The drug developed here will be used for the treatment of breast cancer, osteoporosis, and other estrogen dependent hormonal disorders.